Division of Experimental Therapy, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
Mod Pathol. 2009 Nov;22(11):1401-14. doi: 10.1038/modpathol.2009.112. Epub 2009 Jul 24.
Mucinous carcinoma is considered a distinct pathological entity. However, mucinous tumours can be divided into a least two groups: mucinous A (or paucicellular) and mucinous B (or hypercellular). Mucinous B cancers display histological features that significantly overlap with those of neuroendocrine carcinomas. We investigate using genome-wide oligonucleotide microarrays whether mucinous A, mucinous B and neuroendocrine carcinomas are entities distinct from histological grade- and molecular subtype-matched invasive ductal carcinomas of no special type. Mucinous A and B and five neuroendocrine carcinomas were of luminal A subtype, whereas one neuroendocrine tumour was of luminal B phenotype. When analysed in conjunction with grade- and molecular subtype-matched invasive ductal carcinomas, hierarchical clustering analysis showed that the majority of mucinous and neuroendocrine cancers formed a separate cluster. Significance analysis of microarrays identified 3155 genes differentially expressed between mucinous/ neuroendocrine carcinomas and grade- and molecular subtype-matched invasive ductal carcinomas (false discovery rate <0.85%), and revealed that genes associated with connective tissue/extracellular matrix were downregulated in mucinous/neuroendocrine cancers compared to invasive ductal carcinomas. When subjected to hierarchical clustering analysis separately, mucinous A cancers formed a discrete subgroup, whereas no separation was observed between mucinous B and neuroendocrine cancers. In fact, significance of microarray analysis showed no transcriptomic differences between mucinous B and neuroendocrine cancers, whereas mucinous A cancers displayed 89 up- and 26 downregulated genes when compared with mucinous B (false discovery rate <1.15%) and 368 up- and 48 downregulated genes when compared to neuroendocrine carcinomas (false discovery rate <1.0%). Our results provide circumstantial evidence to suggest that mucinous and neuroendocrine carcinomas are transcriptionally distinct from histological grade- and molecular subtype-matched invasive ductal carcinomas, and that luminal A breast cancers are a heterogeneous group of tumours. These findings support the contention that mucinous B and neuroendocrine carcinomas are part of a spectrum of lesions, whereas mucinous A is a discrete entity.
黏液性癌被认为是一种独特的病理实体。然而，黏液性肿瘤可以分为至少两组：黏液性 A（或少细胞性）和黏液性 B（或多细胞性）。黏液性 B 癌显示出与神经内分泌癌显著重叠的组织学特征。我们使用全基因组寡核苷酸微阵列研究是否黏液性 A、黏液性 B 和神经内分泌癌与组织学分级和分子亚型匹配的非特殊型浸润性导管癌是不同的实体。黏液性 A 和 B 以及五例神经内分泌癌为 luminal A 亚型，而一例神经内分泌肿瘤为 luminal B 表型。当与组织学分级和分子亚型匹配的浸润性导管癌一起分析时，层次聚类分析显示大多数黏液性和神经内分泌癌形成一个单独的簇。微阵列的显著性分析确定了 3155 个在黏液性/神经内分泌癌与组织学分级和分子亚型匹配的浸润性导管癌之间差异表达的基因（错误发现率<0.85%），并表明与结缔组织/细胞外基质相关的基因在黏液性/神经内分泌癌中下调与浸润性导管癌相比。当分别进行层次聚类分析时，黏液性 A 癌形成了一个离散的亚群，而黏液性 B 癌和神经内分泌癌之间没有分离。事实上，微阵列分析的显著性表明黏液性 B 癌和神经内分泌癌之间没有转录组差异，而与黏液性 B 癌相比，黏液性 A 癌显示出 89 个上调和 26 个下调基因（错误发现率<1.15%），与神经内分泌癌相比显示出 368 个上调和 48 个下调基因（错误发现率<1.0%）。我们的结果提供了间接证据表明，黏液性和神经内分泌癌在转录水平上与组织学分级和分子亚型匹配的浸润性导管癌不同，并且 luminal A 乳腺癌是一组异质性肿瘤。这些发现支持这样一种观点，即黏液性 B 癌和神经内分泌癌是病变谱的一部分，而黏液性 A 癌是一个离散的实体。
